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<div class='row'> <div class='small-12 columns'> <h2><a href="/review_series">Review Series</a></h2> </div> </div> <div class='row'> <div class='non-col'> <h3>Microbiome in Health and Disease</h3> <h4>Series edited by Eugene B. Chang</h4> <p>Host-microbe interactions are increasingly recognized for their roles in promoting health as well as in disease pathogenesis. This in-progress series was designed by current JCI Associate Editor Eugene B. Chang to highlight recent advances and challenges in understanding the human microbiome across different organ systems as well as the outlook for microbiome-targeted therapeutics.</p> </div> </div> <div class='row'> <div class='small-12 columns'> <h4>Articles in series</h4> </div> </div> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/184314">The microbiome as a modulator of neurological health across the maternal-offspring interface</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/184314">Stephanie B. Orchanian, Elaine Y. Hsiao</a> <a class='hide-for-small show-more' data-reveal-id='article45776-more' href='#'> <div class='article-authors'> Stephanie B. Orchanian, Elaine Y. Hsiao </div> </a> <span class='article-published-at'> Published February 17, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/4">135(4)</a>:e184314. <a href="https://doi.org/10.1172/JCI184314">https://doi.org/10.1172/JCI184314</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/184314">Text</a> | <a href="/articles/view/184314/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI184314' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/184314/figure/1' ref='group' title='Maternal gut microbiome modulates the maternal and fetal brain. Environmental risk factors, including diet, stress, infection, and xenobiotics, can shape the composition and function of the maternal gut microbiome in ways that impact its interactions with the nervous system in both mother and developing offspring.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/184000/184314/small/JCI184314.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45776-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/184314">The microbiome as a modulator of neurological health across the maternal-offspring interface</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/184314">Text</a></li> <li><a class="button tiny" href="/articles/view/184314/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>The maternal microbiome is emerging as an important factor that influences the neurological health of mothers and their children. Recent studies highlight how microbial communities in the maternal gut can shape early-life development in ways that inform long-term health trajectories. Research on the neurodevelopmental effects of maternal microbiomes is expanding our understanding of the microbiome-gut-brain axis to include signaling across the maternal-offspring unit during the perinatal period. In this Review, we synthesize existing literature on how the maternal microbiome modulates brain function and behavior in both mothers and their developing offspring. We present evidence from human and animal studies showing that the maternal microbiome interacts with environmental factors to impact risk for neurodevelopmental abnormalities. We further discuss molecular and cellular mechanisms that facilitate maternal-offspring crosstalk for neuromodulation. Finally, we consider how advancing understanding of these complex interactions could lead to microbiome-based interventions for promoting maternal and offspring health.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Stephanie B. Orchanian, Elaine Y. Hsiao</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/184315">Skin microbiome and dermatologic disorders</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/184315">Tiffany C. Scharschmidt, Julia A. Segre</a> <a class='hide-for-small show-more' data-reveal-id='article45717-more' href='#'> <div class='article-authors'> Tiffany C. Scharschmidt, Julia A. Segre </div> </a> <span class='article-published-at'> Published February 3, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/3">135(3)</a>:e184315. <a href="https://doi.org/10.1172/JCI184315">https://doi.org/10.1172/JCI184315</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/184315">Text</a> | <a href="/articles/view/184315/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI184315' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/184315/figure/1' ref='group' title='Schematic of skin histology including appendages and microorganisms. Endogenous and exogenous factors contributing to variation in the human skin microbiome.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/184000/184315/small/JCI184315.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45717-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/184315">Skin microbiome and dermatologic disorders</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/184315">Text</a></li> <li><a class="button tiny" href="/articles/view/184315/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Human skin acts as a physical barrier to prevent the entry of pathogenic microbes while simultaneously providing a home for commensal bacteria and fungi. Microbiome sequencing studies have demonstrated the unappreciated diversity and selectivity of these microbes. Functional studies have demonstrated the impact of specific strains to tune the immune system, sculpt the microbial community, provide colonization resistance, and promote epidermal barrier integrity. Recent studies have integrated the microbiome, immunity, and tissue integrity to understand their interplay in common disorders such as atopic dermatitis. In this Review, we explore microbiome shifts associated with cutaneous disorders with an eye toward how the microbiome can be mined to identify new therapeutic opportunities.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Tiffany C. Scharschmidt, Julia A. Segre</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/184316">Microbial influencers: the airway microbiome鈥檚 role in asthma</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/184316">Young Jin Kim, Supinda Bunyavanich</a> <a class='hide-for-small show-more' data-reveal-id='article45761-more' href='#'> <div class='article-authors'> Young Jin Kim, Supinda Bunyavanich </div> </a> <span class='article-published-at'> Published February 17, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/4">135(4)</a>:e184316. <a href="https://doi.org/10.1172/JCI184316">https://doi.org/10.1172/JCI184316</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/184316">Text</a> | <a href="/articles/view/184316/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI184316' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/184316/figure/1' ref='group' title='Many factors influence the airway microbiome and asthma early and throughout life. Perinatal factors and early-life environmental exposures affect the development of the airway microbiome. Growing up in farm and rural environments has been found to be protective against asthma, while smoking, respiratory infections, and antibiotic use increase asthma risk. All of these environmental factors have been associated with airway dysbiosis. Additional factors, including genetics, obesity, medication use, and smoking, can influence the airway microbiome throughout life.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/184000/184316/small/JCI184316.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45761-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/184316">Microbial influencers: the airway microbiome鈥檚 role in asthma</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/184316">Text</a></li> <li><a class="button tiny" href="/articles/view/184316/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Asthma is a common chronic respiratory disease affecting people of all ages globally. The airway hosts diverse microbial communities increasingly recognized as influential in the development and disease course of asthma. Here, we review recent findings on the airway microbiome in asthma. As relationships between the airway microbiome and respiratory health take root early in life, we first provide an overview of the early-life airway microbiome and asthma development, where multiple cohort studies have identified bacterial genera in the infant airway associated with risk of future wheeze and asthma. We then address current understandings of interactions between environmental factors, the airway microbiome, and asthma, including the effects of rural/urban environments, pet ownership, smoking, viral illness, and antibiotics. Next, we delve into what has been observed about the airway microbiome and asthma phenotypes and endotypes, as airway microbiota have been associated with asthma control, severity, obesity-related asthma, and treatment effects as well as with type 2 high, type 2 low, and more newly described multi-omic asthma endotypes. We then discuss emerging approaches to shape the microbiome for asthma therapy and conclude the Review with perspectives on future research directions.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Young Jin Kim, Supinda Bunyavanich</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/184321">The gut microbiome and cancer response to immune checkpoint inhibitors</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/184321">Francesca S. Gazzaniga, Dennis L. Kasper</a> <a class='hide-for-small show-more' data-reveal-id='article45726-more' href='#'> <div class='article-authors'> Francesca S. Gazzaniga, Dennis L. Kasper </div> </a> <span class='article-published-at'> Published February 3, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/3">135(3)</a>:e184321. <a href="https://doi.org/10.1172/JCI184321">https://doi.org/10.1172/JCI184321</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/184321">Text</a> | <a href="/articles/view/184321/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI184321' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/184321/figure/1' ref='group' title='Mechanisms of gut bacteria鈥搈ediated antitumor immunity. (A) E. faecium, E. hirae, E. durans, and E. mundtii release orthogolgs of SagA, a peptidoglycan hydrolase that breaks muramyl bonds in peptidoglycan of other gut bacteria to release GMDP. GMDP signals through NOD2 on myeloid cells to increase transcription of IL-1b and NLRP3 and increase granzyme B+ (GZMB+) CD8+ T cells in the tumor (7). Whether GMDP released by gut bacteria travel from the tumor or immune cells from the gut that have been exposed to GMDP travel to the tumors is unknown. (B) C. cateniformis contains a surface metabolite that suppresses PD-L2 expression on MHCII+CD11b+ and MHCII+CD11c+ immune cells in the mesenteric and tumor-draining lymph nodes (MLNs and dLNs). Blockade of PD-L2/RGMb interactions increases tumor-infiltrating GZMB+ and IFN-纬+CD8+ T cells in the tumors to promote antitumor immunity to anti鈥揚D-L1 (8). How C. cateniformis suppresses PD-L2, whether the microbial surface metabolite or cells that interact with C. cateniformis travel to the dLN, and how the gut microbiome impacts RGMb expression are unknown. (C) A. mucinophila and other bacteria that increase in abundance on a high-fiber diet release c-di-AMP and other products. These products signal through cGAS/STING in monocytes, stimulating antitumor macrophages and releasing type 1 IFNs that stimulate NK cells to release XCL1 and CCL5 and increase tumor-infiltrating dendritic cells to release IL-15 and its receptor IL-15RA. This monocyte-NK-DC crosstalk promotes antitumor responses to anti鈥揚D-1 (55). Whether microbially derived STING agonists or monocytes that have interacted with microbially derived STING agonists in the gut travel to the tumors is unknown. (D) Gut bacteria sensitive to oral metronidazole release TMA, which gets converted into TMAO in the liver, enters the blood stream, and stimulates tumor-associated macrophages to increase IFN-纬+ TNF-伪+ CD8+ and CD4+ T cells in the tumor in a type 1 IFN-dependent manner; this increases response of pancreatic ductal adenocarcinoma (PDAC) tumors to anti鈥揚D-1 therapy (40). (E) L. rhamnosus GG was also shown to signal through cGAS/STING on dendritic cells to release IFN-尾 and increase IFN-纬+CD8+ T cells in tumors, promoting antitumor immunity to anti鈥揚D-1 treatment (10). The identity of the microbial metabolite from L. rhamnosus GG, and whether the metabolite or cells that interacted with L. rhamnosus GG travel from the gut to the tumor, are unknown. Furthermore, it is unclear why L. rhamnosus GG promotes antitumor immunity in some conditions, but not others (10, 14).'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/184000/184321/small/JCI184321.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45726-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/184321">The gut microbiome and cancer response to immune checkpoint inhibitors</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/184321">Text</a></li> <li><a class="button tiny" href="/articles/view/184321/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy, yet only a fraction of patients respond. Remarkably, gut bacteria impact the efficacy of ICIs in fighting tumors outside of the gut. Certain strains of commensal gut bacteria promote antitumor responses to ICIs in a variety of preclinical mouse tumor models. Patients with cancer who respond to ICIs have a different microbiome compared with that of patients who don鈥檛 respond. Fecal microbiota transplants (FMTs) from patients into mice phenocopy the patient tumor responses: FMTs from responders promote response to ICIs, whereas FMTs from nonresponders do not promote a response. In patients, FMTs from patients who have had a complete response to ICIs can overcome resistance in patients who progress on treatment. However, the responses to FMTs are variable. Though emerging studies indicate that gut bacteria can promote antitumor immunity in the absence of ICIs, this Review will focus on studies that demonstrate relationships between the gut microbiome and response to ICIs. We will explore studies investigating which bacteria promote response to ICIs in preclinical models, which bacteria are associated with response in patients with cancer receiving ICIs, the mechanisms by which gut bacteria promote antitumor immunity, and how microbiome-based therapies can be translated to the clinic.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Francesca S. Gazzaniga, Dennis L. Kasper</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> </div> <div class='large-2 medium-3 hide-for-small columns' style='padding: 12px 9px 12px 9px;'> <div style='width:100%; text-align: center;'> <div id='jci-interior-skyscraper-right-col'> <span class='secondary label'>Advertisement</span> <script> try { googletag.cmd.push(function () { googletag.display('jci-interior-skyscraper-right-col'); }); } catch(e){} </script> </div> </div> </div> </div> </div> </div> </div> </div> <div id='footer'> <div class='row panel-padding'> <div class='small-6 columns'> <div id='social-links'> <a onclick="trackOutboundLink('/twitter?ref=footer');" href="/twitter"><img title="Twitter" src="/assets/social/twitter-round-blue-78025a92064e3594e44e4ccf5446aefeafba696cd3c8e4a7be1850c7c9f62aba.png" /></a> <a onclick="trackOutboundLink('/facebook?ref=footer');" href="/facebook"><img title="Facebook" src="/assets/social/facebook-round-blue-2787910d46dcbdbee4bd34030fee044e5a77cfda2221af9191d437b2f5fadeb1.png" /></a> <a href="/rss"><img title="RSS" src="/assets/social/rss-round-color-6f5fa8e93dc066ee4923a36ba6a7cb97d53c5b77de78a2c7b2a721adc603f342.png" /></a> </div> <br> Copyright © 2025 <a href="http://www.the-asci.org">American Society for Clinical Investigation</a> <br> ISSN: 0021-9738 (print), 1558-8238 (online) </div> <div class='small-6 columns'> <div class='row'> <div class='small-12 columns'> <h4 class='notices-signup'>Sign up for email alerts</h4> <form action='https://notices.jci.org/subscribers/new' method='get'> <input name='utm_source' type='hidden' value='jci'> <input name='utm_medium' type='hidden' value='web'> <input name='utm_campaign' type='hidden' value='email_signup'> <input name='utm_content' type='hidden' value='footer'> <div class='row'> <div class='small-12 medium-9 columns'> <input name='email_address' placeholder='Your email address' required type='text'> </div> <div class='small-12 medium-3 columns'> <input class='button tiny orange' type='submit' value='Sign up'> </div> </div> </form> </div> </div> </div> </div> </div> </div> <script src="/assets/application-27f18b5fe3b7302e5b3e3c6d7cf9bb3f54759fad32679209f5aef429b89f3aef.js"></script>  <script src="//s7.addthis.com/js/300/addthis_widget.js#pubid=ra-4d8389db4b0bb592" async="async"></script> <script src="//d1bxh8uas1mnw7.cloudfront.net/assets/embed.js" async="async"></script>  </body> </html>